Class III anti-arrhythmic agents may be categorized as having the ability to markedly prolong dog Purkinje fiber action potential duration without producing significant changes in maximal upstroke velocity. Unlike Class I anti-arrhythmic agents, a pure Class III agent displays no effects on cardiac sodium channels. The electrophysiologic properties of a compound defining a Class III activity profile are observed in vivo as negligible effects on atrial, ventricular and H-V conduction times while producing a marked increase (greater than 20 percent) in both the atrial and ventricular refractory period. In contrast, Class I agents will demonstrate a marked slowing of ventricular conduction velocity, generally without significant changes in the refractory period. Recent reviews of these agents are by Bexton et al., Pharmac. Ther. 17, 315-55 (1982); Vaughan-Williams, J. Clin. Pharmacol. 24, 129-47 (1984) and Thomis et al., Ann. Rep. Med. Chem. 18, 99-108 (1983).
German Offenlegungsschrift 1912848 discloses in Example 5 the intermediate N.sup.1 -(2-isopropylaminoethyl)-N.sup.4 -acetyl-sulfanilamide which is used to produce 1-sulfanilyl-2-imino-3-isopropyl-imidazolidin said to be useful as a hypoglycemic agent.
Silberg et al., ACAD Rep. Populace Romire, Fillala Clug, Studee Cercetari Med., 10 244-52 (1959) discloses p-acetylamino-N-(2-diethylaminoethyl)benzenesulfonamide among other compounds compared in their anti-arrhythmic properties with procainamide.
The Abstracts of Papers to be presented at the 192nd ACS National Meeting, Sep. 7-12, 1986 at Anaheim, Calif. reports Abstract 9 by R. A. Wohl et al. which discloses N-[2-(diethylamino)ethyl]-4-[(methylsulfonyl)amino] benzamide hydrochloride projected as a potential Class III anti-arrhythmic agent.
The Abstracts of Papers to be presented at the 192nd ACS National Meeting, Sep. 7-12, 1986 at Anaheim, Calif. reports Abstract 9 by R. A. Wohl et al. which discloses N-[2-(diethylamino)ethyl]-4-[(methylsulfonyl)amino] benzamide hydrochloride projected as a potential Class III anti-arrhythmic agent.
U.S. Pat. No. 4,544,654 granted Oct. 1, 1985 claims the specific carbonamide named in the preceding paragraph and names the correspondingly substituted sulfonamide species as well as disclosing a genus of sulfonamides corresponding in structure to the generically claimed carbonamides. All the tertiary amines disclosed are said to be Class III antiarrhythmic agents.
EP 0 158 775 published Oct. 23, 1985 presents essentially the same tertiary amine disclosure as the preceding U.S. patent and in addition discloses a genus of secondary amines in which the terminal N-substituted may be an alkyl group containing from 5 to 10 carbon atoms. Secondary amines with less than five carbon alkyl substitution were excluded as inactive Class III antiarrhythmic agents.
U.S. Pat. No. 4,629,739 granted Dec. 16, 1986 claims the secondary amine containing carbonamide derivatives common with EP 0 158 775 and discloses a sulfonamide genus of comparable scope with the claimed carbonamide genus. An N-heptyl substituted sulfonamide compound species is disclosed.